Open AccessEnhancement of esophageal carcinogenesis in acid reflux model rats treated with ascorbic acid and sodium nitrite in combination with or without initiation
Author(s) -
Kuroiwa Yuichi,
Okamura Toshiya,
Ishii Yuji,
Umemura Takashi,
Tasaki Masako,
Kanki Keita,
Mitsumori Kunitoshi,
Hirose Masao,
Nishikawa Akiyoshi
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00649.x
Subject(s) - gastroenterology , sodium nitrite , esophagus , ascorbic acid , reflux esophagitis , nitrite , medicine , esophagitis , reflux , nitrosamine , carcinogenesis , nitric oxide , dysplasia , hyperplasia , carcinogen , chemistry , biochemistry , cancer , food science , nitrate , disease , organic chemistry
Combined treatment with sodium nitrite (NaNO 2 ) and ascorbic acid (AsA) has already been shown to promote rat forestomach carcinogenesis, possibly due to nitric oxide generation under acidic conditions. We hypothesized that a similar effect might occur in the esophagus when the luminal pH is decreased by acid reflux. To clarify this possibility, reflux esophagitis model rats (F344 male) were coadministered 0.2% NaNO 2 in the drinking water and 1% AsA in the diet. After 32 weeks of the combined treatment, a significant increase in the incidence of epithelial hyperplasias of the lower‐middle and lowest parts of the esophagus were observed compared with the basal‐diet group, along with exacerbation of dysplasia and extension of the lesions. Additionally, one squamous cell papilloma was found only in the combined‐treatment group. Subsequently, we confirmed the enhancing effects of NaNO 2 and AsA cotreatment in the rat N ‐bis(2‐hydroxypropyl)nitrosamine‐initiated esophageal tumorigenesis model. The incidence of hyperplasia was enhanced in all segments, along with the incidence and multiplicity of squamous cell papillomas in the lowest segment of the esophagus. Thus, the data demonstrate that combined treatment with NaNO 2 and AsA exerts promoting effects on rat esophageal carcinogenesis under acid reflux conditions, as in the forestomach. These findings suggest that the risk of excessive intake of a combination of nitrite and antioxidants for esophageal carcinogenesis is appreciable, particularly in patients with reflux esophagitis. ( Cancer Sci 2008; 99: 7–13)